Stress-Inducible Regulation of Heat Shock Factor 1 by the Deacetylase SIRT1
Northwestern University · Åbo Akademi University · +4 more institutions
Abstract
Heat shock factor 1 (HSF1) is essential for protecting cells from protein-damaging stress associated with misfolded proteins and regulates the insulin-signaling pathway and aging. Here, we show that human HSF1 is inducibly acetylated at a critical residue that negatively regulates DNA binding activity. Activation of the deacetylase and longevity factor SIRT1 prolonged HSF1 binding to the heat shock promoter Hsp70 by maintaining HSF1 in a deacetylated, DNA-binding competent state. Conversely, down-regulation of SIRT1 accelerated the attenuation of the heat shock response (HSR) and release of HSF1 from its cognate promoter elements. These results provide a mechanistic basis for the requirement of HSF1 in the…
Citation impact
- FWCI
- 30.40
- Percentile
- 100%
- References
- 23
Authors
5- SDSandy D. WesterheideCorresponding
Northwestern University, Åbo Akademi University, Turku Centre for Computer Science, University of Florida, Rice Institute, Turku Centre for Biotechnology
- JAJulius AnckarCorresponding
Northwestern University, Åbo Akademi University, Turku Centre for Computer Science, University of Florida, Rice Institute, Turku Centre for Biotechnology
- SMStanley M. Stevens
Northwestern University, Åbo Akademi University, Turku Centre for Computer Science, University of Florida, Rice Institute, Turku Centre for Biotechnology
- LSLea Sistonen
Northwestern University, Åbo Akademi University, Turku Centre for Computer Science, University of Florida, Rice Institute, Turku Centre for Biotechnology
- RIRichard I. MorimotoCorresponding
Northwestern University, Åbo Akademi University, Turku Centre for Computer Science, University of Florida, Rice Institute, Turku Centre for Biotechnology
Topics & keywords
- HSF1
- Heat shock factor
- Cell biology
- Heat shock
- Hsp70
- Heat shock protein
- Acetylation
- Chemistry